Sarguru Subash
Associate Professor Department of Veterinary PathobiologyResearch and Scholarly Interests
Bacterial urinary tract infection (UTI) is a major global public health problem. Uropathogenic Escherichia coli is the predominant causative agent of UTI. Other clinically significant etiological agents of UTI include Klebsiella pneumoniae, Proteus mirabilis, and Staphylococcus species. Annual estimates for the incidence of UTI are ~11 million and ~150 million in the United States and around the world, respectively. High incidence of UTI coupled with an alarming increase in antibiotic resistant uropathogens underscore the immediate need for development of novel strategies to mitigate UTI.
We study the fitness and virulence mechanisms involved in the pathogenesis of bacterial UTI to identify novel targets that could be harnessed to develop therapeutic or prevention strategies against this ubiquitous infectious condition. We use a combination of bacteriological, biochemical, genetic, and functional genomic approaches, in conjunction with a mouse model, a non-human primate model, and ex vivo and in vitro models to study key aspects of host-uropathogen interaction during UTI.
Education
- PhD: Comparative Medicine and Integrative Biology, August 2006 − May 2011
College of Veterinary Medicine, Michigan State University, East Lansing, MI (Mentor: Dr. Martha Mulks, Professor)
- BVSc: Bachelor of Veterinary Science (equivalent to DVM), October 2000 − December 2005
Madras Veterinary College, Tamil Nadu Veterinary and Animal Sciences University, Chennai, India
Experience
- Assistant Professor, August 2018 − Present
Department of Veterinary Pathobiology, Texas A&M College of Veterinary Medicine & Biomedical Sciences, College Station, TX
- Assistant Professor, October 2015 − July 2018
Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, NC
- Post-doctoral Fellow in the laboratory of Dr. Harry Mobley, June 2011 – September 2015
- Research Scholars Fellow, American Urological Association, June 2012 − June 2014
Department of Microbiology & Immunology, University of Michigan Medical School, Ann Arbor MI
- Graduate Research Assistant in the laboratory of Dr. Martha Mulks, January 2007 − May 2011
Department of Microbiology & Molecular Genetics, Michigan State University, East Lansing, MI
- Role of Copper in Urinary Tract Infection (UTI)
- Copper Homeostasis in Bacterial Pathogens
- UTI as Diabetic Complication
Role of Copper in Urinary Tract Infection
We have demonstrated that copper is mobilized to urine as a host response during clinical UTI in patients. A non-human primate model of UTI recapitulates urinary copper mobilization observed in human UTI. Our findings, taken together with reports of fulminant UTI in patients with Menkes disease (who cannot absorb dietary copper), highlight an important and novel biological role for copper in the protection against UTI. Our investigations are focused on defining the mechanism of copper-mediated protection against UPEC colonization, and to determine how copper is mobilized to urine during UTI caused by UPEC. Our findings are anticipated to break new ground to develop novel interventions against UTI.
Copper Homeostasis in Bacterial Pathogens
We are actively pursuing the mechanisms utilized by various bacterial pathogens to maintain copper homeostasis. We are using both forward and reverse genetic methods, complemented by proteomics to elucidate how bacterial pathogens respond, adapt and survive under copper stress. Knowledge of these processes are critical to understand how host-derived copper in involved in limiting bacterial growth during infection and to develop strategies to augment the toxicity of endogenous copper to bacterial pathogens.
UTI as Diabetic Complication
People with diabetes are highly susceptible to UTI. In the United States alone, almost 1 in 10 people (29.1 million) were diabetic in 2012. We are developing advanced models to understand diabetes-induced changes in the urinary tract during health and disease. By using small molecules, we can now distinguish the effects of increased urinary glucose-fueled bacterial overgrowth from diabetes-induced changes in the urinary tract that increases susceptibility to UTI.
VTPB405: Microbiology for Biomedical Sciences
This upper level undergraduate course is designed to take the learners through an immersive journey in the microbial world. This lecture- and laboratory- based 4-credit course is designed to provide a learning opportunity for BIMS students to master the fundamentals of microbiology and infectious diseases. Laboratory modules are designed to enhance experiential learning, reinforce and develop the concepts discussed in lectures. Instructors will offer this course in a welcoming and intellectually-engaging setting that facilitates achievement of learning objectives. All students are invited to actively participate in lectures and labs to provide an enriching educational experience that involves peer-learning. This course is offered every Fall.
VTMI689: Bacteria in Health and Disease in Spring
This lecture-based 3-credit course is a learning opportunity for Graduate students to master the fundamental roles of bacteria in maintaining health and causing disease in various organ systems. This course is designed for Graduate students engaged in dissertation research on host-pathogen interaction, and Masters students interested in pursuing professional programs in Health Sciences. We discuss the mechanisms utilized by important commensal and pathogenic bacteria in humans and animals, in their respective roles. We will also explore the innate and adaptive immune mechanisms, and antimicrobial chemotherapy against bacterial pathogens. This course is offered every Spring.
Doctoral Degree
- 2019-Present: Kaitlin Casanova
- 2016-Present: Amanda Hyre
Masters’ Degree
- 2018-Present: Aswin Hanagal
Staff Scientist
- 2019-Present: Panatda Saenkham, PhD
Rotation Students
- 2019 Spring: Kaitlin Casanova, Rotation Student
- 2018 Fall: Christian Mitchell, Rotation Student
Undergraduate Students & Interns
- 2018-Present: Chaitali Botcha, Undergraduate Student